Effects of cobalt and bicuculline on focal microstimulation of rat pallidal neurons in vivo
Effects of cobalt and bicuculline on focal microstimulation of rat pallidal neurons in vivo
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DOI：
10.1016/j.brs.2008.05.001
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发表时间：
2008-07-01
影响因子：
7.7
通讯作者：
Hutchison, William D.
中科院分区：
文献类型：
--
作者：
Chin, Gordon D.;Hutchison, William D.
背景：基底节区深部脑刺激（DBS）是治疗运动障碍的有效方法；然而，其作用机制仍然知之甚少。由于高频电刺激（HFS）优先激活纤维，DBS作用的一种假设是轴突末端局部释放的递质抑制了人类术中记录的自发尖峰效应。我们假设阻断突触前递质的释放会减少任何刺激诱导的效应，阻断突触后GABA受体会降低HFS的抑制作用。方法在麻醉大鼠42个单白球（GP）单元注射突触阻断剂氯化钴（100 mM）和二环氯胺（12 μ g/ μ L）前后，通过记录电极或相邻电极传递短时间HFS （2-37 μ A， 0.5秒，300 Hz）的神经元反应。结果对HFS训练的反应主要表现为短暂性（约350毫秒）的抑制，但也有较晚的反应（约1 ~ 2秒）和反弹爆发。在研究的43个神经元中，有4个被观察到兴奋。注射任何一种突触阻断剂后，短暂抑制的神经元的反应减弱了47%，部分支持局部γ -氨基丁酸释放假说。双库兰和钴均能减弱迟发性反应和反弹性爆发反应，但有1例双库兰能增强迟发性抑制反应。hfs诱导的兴奋反应未被突触阻滞剂改变，提示直接刺激GP神经元的突触后元件。结论HFS可局部抑制GP神经元的染色体区活性，刺激轴突和活性树突。这些观察结果有助于阐明DBS的机制。英国皇家版权所有(c) 2008由爱思唯尔公司出版。版权所有。
Background Deep brain stimulation (DBS) administered in the basal ganglia is ail effective therapy for movement disorders; however, the mechanism(s) of action remain poorly understood.Objective Because high-frequency electrical stimulation (HFS) preferentially activates fibers, one hypothesis of DBS action is that local release of transmitters from axon terminals underlies the inhibitory effects on spontaneous spiking observed in human intraoperative recordings. We hypothesize that blocking presynaptic release of transmitters will reduce any stimulation-induced effect and blocking of postsynaptic GABA receptors will reduce the inhibitory effect of HFS.Methods We recorded neuronal responses after short HFS trains (2-37 mu A, 0.5 seconds, 300 Hz) delivered through the recording electrode or via an adjacent electrode in 42 single globus pallidus (GP) units of anesthetized rats before and after injection of the synaptic blockers cobalt chloride (100 mM) and bicuculline methiodide (12 mu g/mu L).Results Responses to HFS trains were mainly transient (similar to 350 milliseconds) inhibition of firing, but a late response (similar to 1-2 seconds) and rebound burst were also found. Excitation was observed in 4 of 43 neurons studied. Neurons with transient inhibition had the response attenuated by 47% after injection of either synaptic blocker, in part supporting the local gamma-aminobutyric acid release hypothesis. Bicuculline methiodide and cobalt attenuated the late response as well as the rebound burst response, but the late inhibitory response was increased by bicuculline methiodide in one case. HFS-induced excitatory responses were not altered by synaptic blockers Suggesting direct stimulation of postsynaptic elements of GP neurons.Conclusions The results indicate HFS induces the local inhibition of ongoing activity of the somal region of GP neurons as well as the stimulation of axons and active dendrites. These observations serve to shed light on the mechanism(s) of DBS. Crown Copyright (c) 2008 Published by Elsevier Inc. All rights reserved.